Prostaglandin E2 (abbreviated as PGE2) has been known as a metabolite in the arachidonate cascade. It has been known that PGE2 possesses cyto-protective activity, uterine contractive activity, a pain-inducing effect, a promoting effect on digestive peristalsis, an awakening effect, a suppressive effect on gastric acid secretion, hypotensive activity and diuretic activity and so on.
A recent study has proved existence of various PGE subtype receptors possessing a different physical role from each other. At present, four receptor subtypes are known and they are called EP1, EP2, EP3, and EP4 (Negishi M., et al., J. Lipid Mediators Cell Signaling, 12, 379-391 (1995)).
It is thought that EP2 subtype receptor relates to inhibition of producing TNF-α and acceleration of producing IL-10. Therefore, the compounds which can bind on EP2 subtype receptor are expected to be useful for the prevention and/or treatment of immune diseases (e.g., autoimmune diseases such as amyotrophic lateral sclerosis (ALS), multiple sclerosis, Sjogren's syndrome, rheumatoid arthritis and systemic lupus erythematosus etc., and rejection after organ transplantation), allergic diseases (e.g., asthma, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, food allergy), neuronal cell death, dysmenorrhea, premature birth, abortion, baldness, retinal neuropathy such as glaucoma, erectile dysfunction, arthritis, pulmonary injury, pulmonary fibrosis, pulmonary emphysema, bronchitis, chronic obstructive pulmonary disease, hepatic injury, acute hepatitis, liver cirrhosis, shock, nephritis (acute nephritis, chronic nephritis), renal failure, circulatory diseases (e.g., hypertension, myocardial ischemia, chronic arterial obstruction, vibration disease), systemic inflammatory response syndrome, sepsis, hemophagocytosis syndrome, macrophage activation syndrome, still disease, Kawasaki Disease, burn, systemic granuloma, ulcerative colitis, Crohn disease, hypercytokinemia at dialysis, multiple organ failure, and bone diseases (e.g., fracture, refracture, intractable fracture, nonunion, pseudarthrosis, osteomalacia, Paget's disease of bone, ankylosing spondylitis, bone metastasis, osteroarthritis and destruction of bone/cartilage due to these analogous diseases) etc. It is also considered that the compounds are useful as an agent for accelerating the osteogenesis/cure after bone surgery (e.g., fracture, bone graft, artificial arthrogenesis, spinal fusion, surgery for multiple myeloma, lung cancer, breast cancer, etc., other bone repair) or substitute treatment for bone grafting. It is further considered that the compounds are useful agents for accelerating the regeneration of peridontium in periodontal disease etc.
As an 8-azaprostaglandin derivative, for example, compounds represented by formula (A):

(wherein QA is selected from the group consisting of —COOR3A, tetrazol-5-yl and —CONHR4A;
AA is a single or cis double bond;
BA is a single or trans double bond;
UA is

R2A is selected from the group consisting of α-thienyl, phenyl, phenoxy, monosubstituted phenyl and monosubstituted phenoxy, said substituents being selected from the group consisting of chloro, fluoro, phenyl, methoxy, trifluoromethyl and alkyl having from one to three carbon atoms;
R3A is selected from the group consisting of hydrogen, alkyl having from one to five carbon atoms, phenyl and p-biphenyl;
R4A is selected from the group consisting of —COR5A and —SO2R5A; said R5A being selected from the group consisting of phenyl and alkyl having from one to five carbon atoms.), a C5 epimer thereof, or an alkali, alkaline earth or ammonium salt of the compound having a carboxylate or tetrazol-5-yl group is described (ref. Japanese published unexamined application No. 53-21159 (U.S. Pat. No. 4,177,346)).
Furthermore, in the specification, a compound represented by formula (A′):
(wherein, WA is selected from the group consisting of —COOR3A, tetrazol-5-yl, N-(acyloxymethyl)tetrazol-5-yl (having from two to five carbon atoms in the acyloxy group), N-(phthalidyl)tetrazol-5-yl and N-(tetrahydropyran-2-yl)-tetrazol-5-y, and the other symbol have the same meanings as described above.), a C5 epimer thereof, or an alkali, alkaline earth or ammonium salt of the compound having a carboxylate or tetrazol-5-yl group is described.
Moreover, a pyrrolidone represented by formula (B):
(wherein R1B represents a straight or branched chain, saturated or unsaturated, aliphatic hydrocarbon radical having up to 10 carbon atoms, or a cycloaliphatic hydro-carbon radical having 3 to 7 carbon atoms, which radicals may be unsubstituted or substituted by one or more of the following:a) a straight or branched chain alkoxy-, alkylthio-, alkenyloxy- or alkenylthio group of up to 5 carbon atoms,b) a phenoxy group which may carry one or two substituents selected from optionally halogenated alkyl groups of 1 to 3 carbon atom(s), halogen atoms, optionally halogenated phenoxy groups, and alkoxy groups of 1 to 4 carbon atoms,c) a furyloxy, thienyloxy or benzyloxy group which may carry, on the nucleus, one or two substituents selected from optionally halogenated alkyl groups of 1 to 3 carbon atom(s), halogen atoms and alkoxy groups of 1 to 4 carbon atoms,d) a trifluoromethyl or pentafluoroethyl group,e) a cycloalkyl group of 3 to 7 carbon atoms,f) a phenyl, thienyl or furyl group which may carry one or two substituents selected from optionally halogenated alkyl groups of 1 to 3 carbon atom(s), halogen atoms, and alkoxy groups of 1 to 4 carbon atoms,
R2B represents a straight or branched chain, saturated or unsaturated, aliphatic or cycloaliphatic hydrocarbon radical having up to 6 carbon atoms, or an araliphatic hydrocarbon radical having 7 or 8 carbon atoms, and
nB represents the integer two, three or four), corresponding free acids thereof, or a physiologically tolerable metal or amine salt thereof is described (ref. Japanese published unexamined application No. 52-5764 (DT 2,528,664)).
In the other specification, a pyrrolidone of the same kind is described (ref. Japanese published unexamined application No. 52-73865 (BE 849,346) and Japanese published unexamined application No. 52-133975 (BE 854,268)).
Moreover, a compound represented by formula (c):
(wherein X1C and X2C are, independently, CH2 or CO, X3C is a nitrogen atom or CH, RC is a hydrogen atom or hydroxyl, R1C and R2C are, independently, CH2 or CO, R3C is CH2, NH or oxygen atom, R4C is NH, CH2 or CO, R5C is CH2 or NH, R6C is CH2 or CO, mC is between 0 and 4, nC is between 0 and 5.) and a pharmaceutically tolerable salt thereof is described (ref. EP 572,365).
Moreover, a compound represented by formula (D):
(when R1D is a hydrogen atom or ethyl, R2D is a hydrogen atom or methyl, and R3D is hydrogen. When R1D is methyl, R2D is a hydrogen atom and R3D is methyl.) or a pharmaceutically tolerable salt thereof is described. In the other specification, an 8-azaprostanoic acid of the same kind is described (ref. Japanese published unexamined application No. 51-127068, Japanese published unexamined application No. 51-128961 and Japanese published unexamined application No. 52-100467 (GB 1,523,178)).
Moreover, compounds represented by formulae (E), (E′) and (E″):
(wherein RE is ester residue, dotted line is double bond or not, and wavy line is α-configuration or β-configuration.) are described (ref. Japanese published unexamined application No. 51-1461).
Moreover, a prostaglandin derivate represented by formula (F):
(wherein R1F represents hydrogen, methyl or ethyl, R2F, R3F and R4F, which are the same or different, each represents hydrogen or methyl and RF is selected from the groups consisting of:
(wherein R5F represents hydrogen, methyl or ethyl, R6F represents methyl, ethyl or acetyl and R7F and R3F each represents hydrogen or a straight-chain alkyl group having from 1 to 3 carbon atom(s).). With the provisos that, when R7F and R3F represent hydrogen, R5F is methyl or ethyl, or when R5F represents methyl and R2F, R3F, R4F, R7F and R3F all represent hydrogen, R1F represents ethyl.) is disclosed (ref. Japanese published unexamined application No. 52-142060 (BE 852,941)). Furthermore, a prostaglandin derivative of the same kind is described (ref. Japanese published unexamined application No. 51-138671 (BE 839,761)).
Moreover, a racemic compound selected from the group represented by formulae (G) and (G′):
(wherein RG is a hydrogen atom, lower alkyl group having from 1 to 4 carbon atoms, when RG is a hydrogen atom, the compounds may form pharmaceutically acceptable nontoxic salts; Z is trans-double bond or saturated bond; waved line is α-configuration, β-configuration or a mixture thereof.) is disclosed (ref. Japanese published unexamined application No. 51-143663 (BE 841,165)).